The candidate's goal is to pursue an independent research career in the field of lung developmental biology. The candidate was trained as a developmental biologist at UCLA. Her graduate and postdoctoral training involved the use of a variety of molecular and genetic approaches to the study of gene expression in developing neurobiological systems. Her entry into the area of lung biology is relatively recent and represents a new direction for her career. The candidate holds a faculty appointment at the Center for Craniofacial Molecular Biology of the University of Southern California. This highly interactive, state-of-the-art research center has provided full support for the candidate's independent research efforts for the past two and a half years and is committed to her continued pursuit of a research career. The candidate plans to develop her career by acquiring new research skills and increasing her knowledge of lung biology and lung diseases through course work, and through formation of new collaborations and new contacts with clinicians and researchers at USC and elsewhere. The candidate is interested in understanding the mechanisms by which prenatal exposure to maternal smoking affects embryonic and fetal lung development, leading to the observed short and long term effects on the respiratory health of the offspring. Her Research Plan addresses the following hypothesis: Nicotine alters the developmental program of the embryonic lung (including expression of surfactant protein genes) through a mechanism involving nicotinic acetylcholine receptors located on cells of the distal epithelium and stimulation of production of GRP by these same distal epithelial cells. The Specific aims are: 1) to characterize the effect of added nicotine on the development of embryonic mouse lungs grown in serumless culture with respect to specific gene expression, growth, branching morphogenesis and differentiation of epithelial cell types, 2) to determine the nature and location of nicotinic acetylcholine receptors mediating the developmental effects of nicotine in the lung and 3) to test the role of the peptide growth factor GRP and its receptor in mediating the effects of nicotine in embryonic lung.